Medical procedure

ABSTRACT

The use of an intravascular cooling element to induce hypothermia in connection with a medical procedure. According to a first aspect of the present, invention, a coronary bypass procedure is conducted in which a patient&#39;s blood is oxygenated with the patient&#39;s lungs and in which blood is circulated using the patient&#39;s heart or using an intracorporeal pump. The procedure preferably comprises: (a) positioning a heat transfer element in a blood vessel of a patient; (b) cooling the body of the patient to less than 35° C., more preferably 32±2° C., using the heat transfer element; and (c) forming a fluid communicating graft between an arterial blood supply and the coronary artery. The body of the patient is preferably heated to about 37° C. using the heat transfer element subsequent to the step of forming the fluid communicating graft. According to a further aspect of the invention, a hypothermic medical procedure is provided while a patient is in a conscious or semiconscious state, comprising (a) administering a beta-blocking drug to the patient; (b) delivering a heat transfer element to a blood vessel of the patient; and (c) cooling a region of the patient or the body of the patient to less than 35° C. using the heat transfer element.

STATEMENT OF RELATED APPLICATIONS

This application is a continuation-in-part of co-pending U.S. patentapplication Ser. No. 10/714,070, filed Nov. 14, 2003, which is acontinuation of U.S. patent application Ser. No. 10/095,753, filed Mar.11, 2002, now U.S. Pat. No. 6,695,873, which is a divisional of U.S.patent application Ser. No. 09/757,124, filed Jan. 8, 2001, now U.S.Pat. No. 6,540,771, which is a divisional of U.S. patent applicationSer. No. 09/215,038, filed Dec. 16, 1998, now U.S. Pat. No. 6,261,312,which is a continuation-in-part of U.S. patent application Ser. No.09/103,342, filed Jun. 23, 1998, now U.S. Pat. No. 6,096,068, which is acontinuation-in-part of U.S. patent application Ser. No. 09/047,012,filed Mar. 24, 1998, now U.S. Pat. No. 5,957,963, which is acontinuation-in-part of U.S. patent application Ser. No. 09/012,287,filed Jan. 23, 1998, now U.S. Pat. No. 6,051,019. Each of thesedisclosures is hereby incorporated by reference in its entirety.

This application is also a continuation-in-part of co-pending U.S.patent application Ser. No. 10/008,999, filed Dec. 7, 2001, which is adivisional of U.S. patent application Ser. No. 09/539,932, filed Mar.31, 2000, now U.S. Pat. No. 6,491,039, which is a continuation-in-partof Ser. No. 09/306,866 filed May 7, 1999, now U.S. Pat. No. 6,235,048,and Ser. No. 09/373,112, filed Aug. 11, 1999, the latter being acontinuation-in-part of Ser. No. 09/292,532 filed Apr. 15, 1999, whichis a continuation-in-part of 09/103,342 filed Jun. 23, 1998, now U.S.Pat. No. 6,096,068, and Ser. No. 09/052,545 filed Mar. 31, 1998, nowU.S. Pat. No. 6,231,595, and Ser. No. 09/047,012 filed Mar. 24, 1998,now U.S. Pat. No. 5,957,963, the last of which is a continuation-in-partof Ser. No. 09/012,287, filed Jan. 23, 1998, now U.S. Pat. No. 6,051,019issued Apr. 18, 2000, and said Ser. No. 09/306,866 filed May 7, 1999 isa divisional of Ser. No. 09/012,287, filed Jan. 23, 1998, now U.S. Pat.No. 6,051,019. Each of these disclosures is hereby incorporated byreference in its entirety.

FIELD OF THE INVENTION

The present invention relates to the use of an intravascular coolingelement to induce hypothermia in connection with medical procedures.

BACKGROUND OF THE INVENTION

A number of approaches have been developed for treating coronary arterydisease. In less severe cases, it is often sufficient to merely treatthe symptoms with pharmaceuticals or to treat the underlying causes ofthe disease with lifestyle modification. In more severe cases, thecoronary blockage can be treated endovascularly or percutaneously usingtechniques such as balloon angioplasty, atherectomy, laser ablation,stents, and the like.

In cases where these approaches have failed or are likely to fail, it isoften necessary to perform a coronary artery bypass graft procedure(“coronary bypass procedure”). In this procedure, direct access to theheart is first achieved. This is usually done by opening the chest bymedian stemotomy and spreading the left and right rib cage apart. Thepericardial sac is then opened to achieve direct access to the heart.Next, a blood vessel or vessels for use in the graft procedure aremobilized from the patient. This usually entails mobilizing either amammary artery or a saphenous vein, although other graft vessels mayalso be used.

A heart-lung or cardiopulmonary bypass is then performed. This procedureusually entails arterial and venous cannulation, connecting thebloodstream to a cardiopulmonary bypass system, cooling the body toabout 32 degrees Celsius, cross clamping the aorta, and cardioplegicperfusion of the coronary arteries to arrest and cool the heart to about4 degrees Celsius.

The arrest or stoppage of the heart is generally carried out because theconstant pumping motion of the beating heart makes surgery upon theheart difficult. Cooling the body protects the organs from ischemia (acondition in which a tissue or organ does not receive a sufficientsupply of blood), reduces the cardiac output requirement, and increasesthe systemic vascular resistance, which helps maintain perfusion andreduces the cardiopulmonary circuit primary volume.

Once cardiac arrest is achieved, a graft (or grafts) is attached to therelevant portions of a coronary artery (or arteries) followed by weaningfrom the cardiopulmonary bypass, restarting the heart, anddecannulation. Finally the chest is closed.

After arresting the heart, the heart muscle, or myocardium, is protectedand supported so that it does not suffer cellular or nerve damage thatwould prevent the heart from working properly when it is started again.There are two important aspects to the process of myocardial protection:(1) reducing the oxygen demand of the heart muscle; and (2) adequatelyoxygenating the heart muscle and maintaining the proper chemical balanceso that cellular damage does not occur. One common technique for doingso is known as cold cardioplegia.

During this procedure, the coronary arteries must be isolated to preventreperfusion of the myocardium with warm oxygenated blood from thecardiopulmonary bypass system that would wash out the cardioplegic agentand prematurely start the heart beating again. The most common way toisolate the coronary arteries is by aortic cross clamping, which isnormally implemented in the following fashion. Before stopping theheart, the patient is prepared by placement of an arterial cannula and avenous cannula, which are connected to the cardiopulmonary bypasssystem. The cardiopulmonary bypass system takes over the functions ofthe heart and the lungs of the patient by pumping and oxygenating theblood while the heart is stopped. Once the cardiopulmonary bypass systemis connected and started, the ascending aorta can be cross-clamped toisolate the coronary arteries from the rest of the systemic arterialcirculation. Then, cardioplegic arrest is induced by injecting 500-1000cc of cardioplegic solution into the aortic root using a needle orcannula which pierces the wall of the ascending aorta upstream of thecross clamp.

Unfortunately, significant complications may result from suchprocedures.

For example, application of an external cross-clamp to a calcified oratheromatous aorta may cause the release of emboli into thebrachiocephalic, carotid or subclavian arteries with seriousconsequences such as strokes.

Systems have been proposed in which the aorta is occluded without crossclamping. For example, U.S. Pat. No. 5,957,879 describes systems thatinclude an aortic occlusion device having a balloon to occlude theascending aorta and a lumen to deliver cardioplegic fluid for arrestingthe patient's heart. The aortic occlusion device replaces theconventional external cross-clamp and is said to reduce the amount ofdisplacement and distortion of the aorta. Nonetheless, distortion is noteliminated, and the risk of emboli release remains present.

Other complications can arise from the cardiopulmonary bypass system,which includes mechanical blood pumps, an oxygenator, a heat exchanger,blood reservoirs and filters, and several feet of tubing to transportthe blood from the patient on the operating table to the heart-lungmachine located nearby and back to the patient. Such systems can causecomplications due to the exposure of blood to foreign surfaces, whichresult in the activation of virtually all the humoral and cellularcomponents of the inflammatory response, as well as some of the slowerreacting specific immune responses. Other complications fromcardiopulmonary bypass include loss of red blood cells and platelets dueto shear stress damage. In addition, cardiopulmonary bypass requires theuse of an anticoagulant, such as heparin. This may, in turn, increasethe risk of hemorrhage. Finally cardiopulmonary bypass sometimesnecessitates giving additional blood to the patient. The additionalblood, if from a source other than the patient, may expose the patientto blood-borne diseases.

Due to the risks noted above, others have attempted to perform acoronary artery bypass graft procedure without occluding the aorta andwithout cardiopulmonary bypass. For example, attempts have been madewherein surgery is performed on a beating heart. The technique ofoperating on the beating heart, however, is difficult, due to the rapidmovement of the heart, and can at present only be applied to singlevessel bypassing procedures. Moreover, partial aortic cross clamping isgenerally implemented, which can dislodge emboli.

In other reported procedures, surgeons have been experimenting with atechnique that involves stopping or nearly stopping the heart andsupporting circulation with a small pump positioned in the patient'svasculature (i.e., an intracorporeal pump). See, for example, M. S.Sweeney, “The Hemopump in 1997: A Clinical, Political, and MarketingEvolution”, Ann. Thorac. Surg, 1999, Vol. 68, pp. 761-3 in which acoronary bypass procedure is described that uses a Medtronic Hemopump®for circulatory support and the patient's own lungs from oxygenation.Esmolol, a short acting beta-blocker, was administered to make the heartmore tranquil during surgery. The interior surface area of the Hemopumpis greatly reduced relative to traditional cardiopulmonary bypasssystems, reducing the complications of such surfaces.

Unfortunately, it can be difficult to provide adequate circulation witha pump of this type, increasing the risk of ischemia. Moreover, whilemany of the dangers associated with cardiopulmonary bypass systems areavoided, certain benefits of such a system are also lost. For example,hypothermia is no longer induced in the patient, which serves to loweroxygen demand and which induces vasoconstriction, supporting perfision.Each of these effects serves to protect the organs from ischemic damage.

Still other techniques have been proposed in which the heart is stoppedor nearly stopped (e.g., placed in a reversible, temporary heart block)by locally delivering drugs, such as beta-blockers. At the same time,the heart is continuously paced by external pacemaker stimulation. Inthis way, alternating periods of heartbeat and heart arrest (e.g., up to15 seconds) can be established, providing the surgeon with shortintervals in which he or she can work on a stilled heart withoutresorting to a pump for supporting circulation. One such system is theTRANSARREST system of Corvascular, Inc., Palo Alto, Calif. Still othermethods are known in which surgery is facilitated by stopping or slowingthe heart though electrical stimulation of the vagus nerve. See, e.g.,U.S. Pat. Nos. 5,913,876 and 6,006,134.

Unfortunately, as in the above case wherein the Hemopump supportscirculation, these techniques result in less than ideal circulation anddo not provide a hypothermic effect, increasing the risk of ischemia.

Medical procedures are also known in which hypothermia is induced in aconscious or semiconscious person, for example, where hypothermia isinduced in a stroke victim to reduce ischemic damage. However, in suchpatients, hypothermia activates the sympathetic nervous system,resulting in a significant norepinephrine response. Norepinephrine, inturn, binds to beta-receptor sites, including those in the heart,causing the heart to beat harder and more rapidly, frequently resultingin cardiac arrythmia and increasing the risk of myocardial ischemia.Norepinephrine also causes peripheral vasoconstriction, frustratingrelief of patient discomfort, for example, by using heating blankets.

SUMMARY OF THE INVENTION

The above and other difficulties associated with the prior art areaddressed by the present invention.

According to a first aspect of the present invention, a coronary bypassprocedure is conducted in which the patient's blood is oxygenated withthe patient's lungs and in which blood is circulated using the patient'sheart or using an intracorporeal pump. The procedure preferablycomprises: (a) positioning a heat transfer element in a blood vessel ofa patient; (b) cooling the body of the patient to less than 35° C., morepreferably 32±2° C., using the heat transfer element; and (c) forming afluid communicating graft between an arterial blood supply and thecoronary artery.

The body of the patient is desirably heated to about 37° C. using theheat transfer element subsequent to the step of forming the fluidcommunicating graft.

Numerous variations are possible. For example, the step of forming afluid communicating graft between the arterial blood supply and thecoronary artery can be performed on a beating heart during bradycardiaof the heart that occurs upon cooling the patient's body.

In another embodiment, the heart can be arrested or nearly arrestedduring at least a portion of the step of forming the fluid communicatinggraft. For example, the heart can be chemically arrested (e.g., usingone or more beta-blockers), or the heart can be electrically arrested.While heart is arrested, the patient's circulation is preferablysupported with a pump positioned in the patient's vasculature. In apreferred embodiment, the pump is at least partially positioned in theleft ventricle and is introduced into the patient through the femoralartery.

In yet another embodiment, the heartbeat is intermittently arrested andstimulated, and at least a portion of the step of forming the fluidcommunicating graft is carried out during periods of heartbeat arrest.For example, the heart can be chemically arrested (e.g., with one ormore beta blockers) and electrically stimulated. Alternatively, theheart can be both electrically arrested and electrically stimulated. Inthis way, the use of a pump can be avoided.

The heat transfer element can be positioned, for example, in the venousvasculature, where it is preferably introduced via the femoral vein.More preferably, the heat transfer element is positioned in the inferiorvena cava via the femoral vein. In this instance, the heat transferelement is preferably about 4 to 5 mm in diameter.

In one preferred embodiment, the heat transfer element is attached tothe distal end of a flexible catheter, and the catheter is used in thestep of positioning the heat transfer element in the blood vessel. Thecatheter is also used to convey chilled or heated fluid to the interiorof the heat transfer element.

The catheter is desirably configured for efficient heat transfer. As anexample, it is preferred that the heat transfer element absorbs at least150 Watts of heat during cooling. To promote efficient heat transfer,the heat transfer element can comprise a plurality of exterior andinterior surface irregularities, wherein the exterior and interiorsurface irregularities are preferably shaped and arranged to createmixing in the blood and in the fluid within the heat transfer element,respectively. In a preferred embodiment, the interior and exteriorsurface irregularities comprise one or more helical ridges and one ormore helical grooves.

In one embodiment, the heat transfer device has a high degree of lateralflexibility and is collapsible, thereby affording an easy insertionprocedure. The device allows high surface area to increase heattransfer.

In one aspect, the invention is directed to a catheter system to changethe temperature of blood by heat transfer to or from a working fluid.The system includes an inflatable inlet lumen and outlet lumen. Theoutlet lumen is coupled to the inlet lumen so as to transfer workingfluid between the two. The outlet lumen has a structure when inflated toinduce turbulence in the blood and/or in the working fluid.

Variations of the system may include one or more of the following. Theinlet lumen and the outlet lumen may be made of a flexible material suchas latex rubber. The outlet lumen may have a structure to induceturbulence in the working fluid when inflated, such as a helical shapewhich may be tapered in a segmented or non-segmented manner. The radiiof the inlet and outlet lumens may decrease in a distal direction suchthat the inlet and outlet lumens are tapered when inflated. A wire maybe disposed in the inlet or outlet lumens to provide shape and strengthwhen deflated.

The thickness of the outlet lumen, when inflated, may be less than about½ mil. The length of the inlet lumen may be between about 5 and 30centimeters. If the outlet lumen has a helical shape, the diameter ofthe helix may be less than about 8 millimeters when inflated. The outerdiameter of the helix of the outlet lumen, when inflated, may be betweenabout 2 millimeters and 8 millimeters and may taper to between about 1millimeter and 2 millimeters. In segmented embodiments, a length of asegment may be between about 1 centimeter and 10 centimeters. The radiiof the inlet and outlet lumens when inflated may be between about 0.5millimeters and 2 millimeters.

The outlet lumen may further include at least one surface feature and/orinterior feature, the surface feature inducing turbulence in the fluidadjacent the outlet lumen and the interior feature inducing turbulencein the working fluid. The surface feature may include one or morehelical turns or spirals formed in the outlet lumen. Adjacent turns mayemploy opposite helicity. Alternatively or in combination, the surfacefeature may be a series of staggered protrusions formed in the outletlumen.

The turbulence-inducing outlet lumen may be adapted to induce turbulencewhen inflated within a free stream of blood when placed within anartery. The turbulence intensity may be greater than about 0.05. Theturbulence-inducing outlet lumen may be adapted to induce turbulencewhen inflated throughout the period of the cardiac cycle when placedwithin an artery or during at least 20% of the period.

The system may further include a coaxial supply catheter having an innercatheter lumen coupled to the inlet lumen and a working fluid supplyconfigured to dispense the working fluid and having an output coupled tothe inner catheter lumen. The working fluid supply may be configured toproduce a pressurized working fluid at a temperature of between about−3° C. and 36° C. and at a pressure below about 5 atmospheres ofpressure. Higher temperatures may be employed if blood heating isdesired.

The turbulence-inducing outlet lumen may include a surface coating ortreatment such as heparin to inhibit clot formation. A stent may becoupled to the distal end of the inlet lumen. The system may be employedto cool or heat volumes of tissue rather than blood.

In embodiments employing a tapered helical outlet lumen, the taper ofthe outlet lumen allows the outlet lumen to be placed in an arteryhaving a radius less than the first radius. The outlet lumen may betapered in segments. The segments may be separated by joints, the jointshaving a radius less than that of either adjacent segment.

In another aspect, the invention is directed to a method of changing thetemperature of blood by heat transfer. The method includes inserting aninflatable heat transfer element into an artery or vein and inflatingthe same by delivering a working fluid to its interior. The temperatureof the working fluid is generally different from that of the blood. Themethod further includes inducing turbulence in the working fluid bypassing the working fluid through a turbulence-inducing path, such thatturbulence is induced in a substantial portion of a free stream ofblood. The inflatable heat transfer element may have aturbulence-inducing structure when inflated.

In another aspect, the invention is directed towards a method oftreating the brain which includes inserting a flexible heat transferelement into an artery from a distal location and circulating a workingfluid through the flexible heat transfer element to inflate the same andto selectively modify the temperature of an organ without significantlymodifying the temperature of the entire body. The flexible, conductiveheat transfer element preferably absorbs more than about 25, 50 or 75watts of heat. The artery may be the common carotid or a combination ofthe common carotid and the internal carotid.

In another aspect, the invention is directed towards a method forselectively cooling an organ in the body of a patient which includesintroducing a catheter into a blood vessel supplying the organ, thecatheter having a diameter of 5 mm or less, inducing free streamturbulence in blood flowing over the catheter, and cooling the catheterto remove heat from the blood to cool the organ without substantiallycooling the entire body. In one embodiment, the cooling removes at leastabout 75 watts of heat from he blood. In another embodiment, the coolingremoves at least about 100 watts of heat from the blood. The organ beingcooled may be the human brain.

The circulating may further include passing the working fluid in throughan inlet lumen and out through an outlet, coaxial lumen. The workingfluid may be a liquid at or well below its boiling point, andfurthermore may be aqueous.

Advantages of the invention include one or more of the following. Thedesign criteria described above for the heat transfer element: smalldiameter when deflated, large diameter when inflated, high flexibility,and enhanced heat transfer rate through increases in the surface of theheat transfer element and the creation of turbulent flow, facilitatecreation of a heat transfer element which successfully achievesselective organ cooling or heating. Because only a selected organ iscooled, complications associated with total body hypothermia areavoided. Because the blood is cooled intravascularly, or in situ,problems associated with external circulation of the blood areeliminated. Also, only a single puncture and arterial vessel cannulationare required which may be performed at an easily accessible artery suchas the femoral, subclavian, or brachial arteries. By eliminating the useof a cold perfusate, problems associated with excessive fluidaccumulation are avoided. In addition, rapid cooling to a precisetemperature may be achieved. Further, treatment of a patient is notcumbersome and the patient may easily receive continued care during theheat transfer process. The device and method may be easily combined withother devices and techniques to provide aggressive multiple therapies.Other advantages will become clear from the description below.

According to a second aspect of the invention, a hypothermic medicalprocedure is provided comprising (a) administering a beta-blocking drugto a patient; (b) delivering a heat transfer element to a blood vesselof a patient; and (c) cooling a region of the patient or the body of thepatient to less than 35° C. using the heat transfer element while thepatient is in a conscious or semiconscious state. Preferably, thebeta-blocking drug is administered after delivering the heat transferelement to the blood vessel. Preferred beta-blocking drugs for thisaspect of the invention include β1 blockers, β1β2 blockers, and αβ1β2blockers. Preferred β1 blockers include acebutolol, atenolol, betaxolol,bisoprolol, esmolol and metoprolol. Preferred β1β2 blockers includecarteolol, nadolol, penbutolol, pindolol, propranolol, sotalol andtimolol. Preferred αβ1β2 blockers include carvedilol and labetalol.

Advantages of the present invention include the elimination of aorticocclusion and cardiopulmonary bypass systems during coronary bypasssurgery. Where beating heart procedures are incorporated, anotheradvantage of the present invention is the promotion of a bradycardia ofthe heart, simplifying surgery.

Another advantage of the present invention include a reduction in therisk of ischemia associated with techniques that provide circulatoryflow rates that are significantly lower than ordinary cardiac output andwith techniques incorporating vasodilatory substances.

Yet another advantage of the present invention is that the risk ofcardiac arrythmia and myocardial ischemia is reduced in connection withmedical procedures that induce hypothermia in conscious or semiconsciouspatents.

The above and other embodiments and advantages of the invention willbecome apparent to those of ordinary skill in the art upon reading thedescription and claims to follow.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic representation of the use of a heat transferelement to cool the body, according to an embodiment of the invention.

FIG. 2 is an elevation view of a mixing inducing heat transfer elementwithin a blood vessel in accordance with an embodiment of the invention.

FIG. 3 is an elevation view of a heat transfer element used inaccordance with an embodiment of the invention.

FIG. 4 a longitudinal section view of the heat transfer element of FIG.3.

FIG. 5 is a side schematic view of an inflatable turbulence-inducingheat transfer element according to an embodiment of the invention, asthe same is disposed within an artery.

FIG. 6 illustrates an inflatable turbulence-inducing heat transferelement according to an alternative embodiment of the inventionemploying a surface area enhancing taper and a turbulence-inducingshape.

FIG. 7 illustrates a tapered joint which may be employed in theembodiment of FIG. 6.

FIG. 8 illustrates a turbulence-inducing heat transfer element accordingto a second alternative embodiment of the invention employing a surfacearea enhancing taper and turbulence-inducing surface features.

FIG. 9 illustrates a type of turbulence-inducing surface feature whichmay be employed in the heat transfer element of the embodiment of FIG.8. In FIG. 9 a spiral feature is shown.

FIG. 10 illustrates another type of turbulence-inducing surface featurewhich may be employed in the heat transfer element of the embodiment ofFIG. 8. In FIG. 10, a series of staggered protrusions are shown.

FIG. 11 is a transverse cross-sectional view of the heat transferelement of the embodiment of FIG. 10.

FIG. 12 illustrates a heat transfer element according to a thirdalternative embodiment of the invention employing a surface areaenhancing taper.

FIG. 13 is a schematic representation of an embodiment of the inventionbeing used to cool the brain of a patient.

DETAILED DESCRIPTION OF THE INVENTION

The present invention now will be described more fully hereinafter. Thisinvention may, however, be embodied in different forms and should not beconstrued as limited to the embodiments set forth herein.

According to one aspect of the present invention, a procedure isprovided by which a surgeon is able to perform a coronary bypassprocedure with hypothermic protection, while at the same time avoidingmany of the disadvantages associated with the use of traditionalexternal cardiopulmonary bypass systems and aortic clamping procedures.

In one embodiment of the present invention, a heat transfer element isprovided within a blood vessel of the body such that blood is cooled invivo upon contact with the heat transfer element.

The heat transfer element can be provided in either arterial or venousblood vessels. One preferred location for the heat transfer element isthe inferior vena cava, which typically ranges from 15 mm to 25 mm indiameter. A preferred method by which the heat transfer element isprovided at this position is via entry at the femoral vein.

FIG. 1 is a schematic representation of the use of a heat transferelement in cooling the body of a patient. The apparatus shown in FIG. 1includes a working fluid supply 10, preferably supplying a chilledaqueous solution, a supply catheter 12 and a heat transfer element 14.The supply catheter 12 may have a substantially coaxial construction. Aninner coaxial lumen within the supply catheter 12 receives coolant fromthe working fluid supply 10. The coolant travels the length of thesupply catheter 12 to the heat transfer element 14 that serves as thecooling tip of the catheter. At the distal end of the heat transferelement 14, the coolant exits an insulated interior lumen and traversesthe length of the heat transfer element 14 in order to decrease thetemperature of the surface of the heat transfer element 14. The coolantthen traverses an outer lumen of the supply catheter 12 so that it maybe disposed of or recirculated. The supply catheter 12 is a flexiblecatheter having a diameter sufficiently small to allow its distal end tobe inserted percutaneously into an accessible blood vessel, shown inFIG. 1 as the right femoral vein. The supply catheter 12 is sufficientlylong to allow the heat transfer element 14 at the distal end of thesupply catheter 12 to be passed through the vascular system of thepatient and placed in the blood vessel of interest, here the inferiorvena cava. The method of inserting the catheter into the patient androuting the heat transfer element 14 into a selected artery or vein iswell known in the art.

In the embodiment of FIG. 1, the narrowest blood vessel encountered bythe heat transfer element as it travels to the inferior vena cava is thefemoral artery, which generally ranges from 5 to 8 mm in diameter.Accordingly, in this embodiment of the invention, the diameter of theheat transfer element is about 4 to 5 mm in diameter.

In order to obtain the benefits associated with hypothermia during acoronary bypass procedure, it is desirable to reduce the temperature ofthe blood flowing within the body to less than 35° C., more preferablybetween 30 and 35° C., and most preferably 32±2° C. Given a typicalblood flow rate of approximately 2.5 to 4 l/min, more typically about3.5 l/min, in the inferior vena cava, the heat transfer elementpreferably absorbs 200 to 300 Watts of heat when placed in this vein, inorder to induce the desired cooling effect. Approximate cooling time is15 to 30 minutes.

Cooling the body to less than 35° C. provides a number of desirableeffects. First, cooling will induce a bradycardia of the heart. Reducedheart rates corresponding to about ⅔ of the normal heart rate are commonat the preferred temperature of 32±2 C. By slowing the beating of theheart, the present invention facilitates surgery during beating heartprocedures. Such procedures are well known in the art. For example, theperformance of coronary surgery on the beating heart is described byBenetti et al in “Coronary Revascularization With Arterial Conduits Viaa Small Thoracotomy and Assisted by Thoracoscopy, Although WithoutCardiopulmonary Bypass”, Cor. Europatum, 4(1): 22-24 (1995), and byWestaby, “Coronary Surgery Without Cardiopulmonary Bypass” in the March,1995 issue of the British Heart Journal. Additional discussion of thissubject matter can be found in Benetti et al, “Direct myocardialrevascularization without extracorporeal circulation. Experience in 700patients”, Chest, 100(2): 312-16 (1991), Pfister et al, “Coronary arterybypass without cardiopulmonary bypass” Ann. Thorac. Surg., 54:1085-92(1992), and Fanning et al, “Reoperative coronary artery bypass graftingwithout cardiopulmonary bypass”, Ann. Thorac. Surg., 55:486-89 (1993).Each of the above articles is hereby incorporated by reference.

Moreover, the general anesthesia associated with coronary bypasstechniques is often accompanied by vasodilation in the patient, whichdecreases organ perfusion and hence increases the risk of ischemia. Thiseffect, however, is combated by the hypothermia induced in accordancewith the present invention, which promotes vasoconstriction.

Cooling the body also protects the organs from ischemic damage due tolow circulatory flow rates or due to emboli formation. For example, aspreviously noted, procedures are known in the art in which (1) the heartis intermittently stopped and restarted or (2) the heart is stopped anda small intracorporeal pump is used to provide circulatory support.These techniques and others like them allow the surgeon to operate on astill or nearly still heart. However, each of these techniques alsoplaces the patient at risk from ischemia. By lowering the bodytemperature of the patient to a preferred temperature of 32±2° C. inaccordance with the present invention, however, the oxygen demand of thebodily tissue, and hence the danger of ischemia associated with theseprocedures, is reduced.

More specifically, with some techniques in which alternating periods ofheartbeat and heart arrest are provided, the heart is stopped or nearlystopped using drugs such as beta-blockers, and a pacing device is usedto cause the heart to beat on demand. An example of one such system isthe TRANSARREST system; Corvascular, Inc., Palo Alto, Calif. In othertechniques, the heart is momentarily stopped or slowed by electricallystimulating the vagus nerve. See, e.g., U.S. Pat. Nos. 5,913,876 and6,006,134, the disclosures of which are hereby incorporated byreference. (As noted in U.S. Pat. No. 5,913,876, one or more heartpacing devices, such as a Pace port-Swann pulmonary artery catheter, maybe inserted in conventional fashion to the patient's heart and used torestore the beating of the heart during the surgery, in the event theheart is slow to revive after a nerve stimulating signal is turned off.)Each of these techniques is associated with a circulatory flow rate thatcan be significantly lower than normal cardiac output.

The risks of ischemia due to low circulatory flow rates, however, arereduced in accordance with an embodiment of the invention. Inparticular, before manipulating the heartbeat of the patient, a heattransfer element is inserted into the vasculature of the patient and thebody temperature of the patient is reduced, preferably to 32±2° C. Asnoted above, by lowering the body temperature, the body's oxygen demandis reduced, decreasing the risk of ischemia. Moreover, a reduction inbody temperature in accordance with the present invention is accompaniedby vasoconstriction, which decreases the circulatory flow rate that isrequired for adequate organ perfusion and consequently further decreasesthe risk of ischemia.

The present invention is also useful in connection with techniques inwhich the heart is stopped or nearly stopped and an intracorporeal pumpis used to support circulation. For example, techniques are known inwhich circulatory support is provided during coronary bypass by a pumppositioned in the patient's aortic valve. See, for example, M. S.Sweeney, “The Hemopump in 1997: A Clinical, Political, and MarketingEvolution”, Ann. Thorac. Surg., 1999, Vol. 68, pp. 761-3, the entiredisclosure of which is hereby incorporated by reference. In thisreference, a coronary bypass operation is described in which esmolol, ashort acting beta-blocker, is administered to calm the heart duringsurgery. A Medtronic Hemopump® is used for circulatory support and thepatient's own lungs are used for oxygenation. At the core of theHemopump is a small, rapidly turning Archimedes screw. The pump assemblyis made of stainless steel and is attached to a silicone rubber inletcannula. The cannula is positioned across the aortic valve and into theleft ventricle. The pump assembly is catheter mounted to facilitateplacement of the pump in its operating position. For example, the pumpassembly is ordinarily inserted into the femoral artery of the thigh,whereupon it is guided to the left ventricle. Once in place, the cannulaacts to entrain blood and feeds it to the pump portion, which then pumpsthe blood into circulation via the aorta. The pump is operated by thecreation of pulsing electromagnetic fields, which cause rotation of apermanent magnet, resulting in operation of the Archimedes screw.Electrical power is provided from a console outside the patient. Thepumping action is axial and continuous (i.e., non-pulsatile). Due to thedesign of the Hemopump, rotational speeds on the order of 10,000 to20,000 rpm can be used to produce blood flow of about four liters perminute or less (depending on the model) without significant hemolysis.Additional details are found in M. C. Sweeney and O. H. Frazier,“Device-supported myocardial revascularization; safe help for sickhearts”, Ann. Thorac. Surg. 1992, 54: 1065-70 and U.S. Pat. No.4,625,712, the entire disclosures of which are hereby incorporated byreference.

This technique and others like it, however, are frequently associatedwith circulatory flow rates (i.e., about 4 l/min or less) that are lowerthan normal cardiac output (i.e., about 5 l/min for many people) placingthe patient at ischemic risk. By lowering the body temperature of thepatient to a preferred range of 32±2° C. in accordance with the presentinvention, however, the blood vessels are constricted and oxygen demandof the bodily tissue is reduced, increasing organ perfusion and reducingthe danger of ischemia for a given circulatory output.

As noted above, in a preferred embodiment of this first aspect of theinvention, the heat transfer element is provided in the inferior venacava, which is accessed via the femoral vein. In contrast, the Hemopumpis preferably provided in the left ventricle, which is accessed via thefemoral artery. In this way, both the heating element and the Hemopumpcan be concurrently placed in the body in a minimally invasive fashion.

According to another aspect of the invention, a hypothermic medicalprocedure is performed on a patient in a conscious or semiconsciousstate. An example of a situation where such a hypothermic medicalprocedure may be performed is one in which a patient has suffered astroke and hypothermia is induced in the brain to reduce ischemicdamage.

Such procedures can be performed either to cool the entire body of thepatient or a region within the patient's body, typically an organ.

The entire body can be cooled using the procedures discussed above. Forexample, the heat transfer element is preferably provided in a venousblood vessel, more preferably the inferior vena cava, to effect coolingof the entire body.

In order to intravascularly regulate the temperature of a selectedregion, the heat transfer element may be placed in a feeding artery ofthe region to absorb or deliver the heat from or to the blood flowinginto the region. The heat transfer element should be small enough to fitwithin the feeding artery while still allowing a sufficient blood flowto reach the region in order to avoid ischemic damage. By placing theheat transfer element within the feeding artery of a region, thetemperature of the region can be controlled, while having less effect onthe remaining parts of the body. Using the brain as an example, thecommon carotid artery supplies blood to the head and brain. The internalcarotid artery branches off of the common carotid to directly supplyblood to the brain. To selectively cool the brain, the heat transferelement is placed into the common carotid artery, or both the commoncarotid artery and the internal carotid artery. The internal diameter ofthe common carotid artery ranges from 6 to 8 mm and the length rangesfrom 80 to 120 mm. Thus, the heat transfer element residing in one ofthese arteries cannot be much larger than 4 mm in diameter in order toavoid occluding the vessel, which would result, for example, in ischemicdamage.

When hypothermia is induced in a patient, less than desirable sideeffects can occur in the patient. For example, hypothermia is known toactivate the sympathetic nervous system in a conscious or semiconsciouspatient, resulting in a significant norepinephrine response.Norepinephrine, in turn, binds to beta sites including those in theheart, causing the heart to beat harder and more rapidly, frequentlyresulting in cardiac arrythmia and increased risk of myocardialischemia. In accordance with an embodiment of the present invention,however, a beta-blocker is administered to the patient. Without wishingto be bound by theory, it is believed that the beta-blocker offsets thenorepinephrine binding noted above. In general, the beta-blocker may beadministered before the patient cooling commences, and preferablyimmediately before patient cooling commences.

Preferred beta-blockers for this aspect of the invention include β1blockers, β1β2 blockers and αβ1β2 blockers. Preferred β1 blockersinclude acebutolol, atenolol, betaxolol, bisoprolol, esmolol andmetoprolol. Preferred β1β2 blockers include carteolol, nadolol,penbutolol, pindolol, propranolol, sotalol and timolol. Preferred αβ1β2blockers include carvedilol and labetalol.

The heightened demand that hypothermia places on the heart of consciousor semiconscious patents may also be relieved, for example, with heatingblankets. However, vasoconstriction limits the heating ability of theheating blankets. Without wishing to be bound by theory, it is believedthat the above-noted production of norepinephrine activatesalpha-receptors, for example, in the peripheral blood vessels, causingthis vasoconstriction. The vasoconstriction can be offset, in accordancewith the present invention, by treating the patient with alpha-blockerswhen indicated, preferably before cooling is initiated. Preferredalpha-blockers include labetalol and carvedilol.

In the various embodiments of the invention, once the medical procedureis completed, the heat transfer element is preferably used to warm thebody back to its normal temperature, i.e., 37° C.

Regarding the construction of the heat transfer element, this componentis ideally a flexible element, allowing it to be placed at the desiredvascular position. For example, the element often has to be passedthough a series of one or more venous or arterial branches, makingflexibility an important characteristic of the heat transfer element.

Further, the heat transfer element is ideally constructed from a highlythermally conductive material such as metal or very thin plastics orpolymers, in order to facilitate heat transfer. The use of a highlythermally conductive material increases the heat transfer rate for agiven temperature differential between the fluid within the heattransfer element and the blood. Highly thermally conductive materials,such as metals, tend to be rigid. Therefore, the design of the heattransfer element should facilitate flexibility in an inherentlyinflexible material.

In general, the magnitude of the heat transfer rate is proportional tothe surface area of the heat transfer element, the temperaturedifferential, and the heat transfer coefficient of the heat transferelement.

Diameter, and hence surface area, of the heat transfer element islimited to avoid significant obstruction of the vein or artery and toallow the heat transfer element to easily pass through the vascularsystem. As noted above, for placement within the inferior vena cava, thecross sectional diameter of the heat transfer element is about 4-5 mm.For placement in the internal carotid artery, the cross sectionaldiameter is about 2 to 3.5 mm. Typically, the length of the heattransfer element for this purpose is about 10 to 30 cm.

When used in cooling mode, decreasing the surface temperature of theheat transfer element can increase the temperature differential.However, the minimum allowable surface temperature is limited by thecharacteristics of blood. Blood freezes at approximately 0° C. When theblood approaches freezing, ice emboli may form in the blood that maylodge downstream, causing serious ischemic injury. Furthermore, reducingthe temperature of the blood also increases its viscosity, which resultsin a small decrease in the value of the convection heat transfercoefficient. In addition, increased viscosity of the blood may result inan increase in the pressure drop within the artery or vein, thuscompromising the flow of blood to the organs. Given the aboveconstraints, it is advantageous to limit the minimum allowable surfacetemperature of the heat transfer element to approximately 5° C. Thisresults in a maximum temperature differential between the blood streamand the heat transfer element of approximately 32° C. when the heattransfer device is used in cooling mode.

Similarly, when in heating mode, increasing the surface temperature ofthe heat transfer element can increase the temperature differential.Analogous to cooling, however, the maximum allowable surface temperatureis limited by the characteristics of blood. In particular, damage toblood components can occur at temperatures of about 45-48° C. and above.Accordingly, it is advantageous to limit the maximum allowable surfacetemperature of the heat transfer element to approximately 44° C. Thisresults in a maximum temperature differential between the blood streamand the heat transfer element of approximately 7° C. when the heattransfer device is used in heating mode.

The mechanisms by which the value of the convection heat transfercoefficient may be increased are complex. However, it is well known thatthe convection heat transfer coefficient increases with the level ofturbulent kinetic energy in the fluid flow. Thus it is advantageous tohave turbulent or mixing blood flow in contact with the heat transferelement.

Specifically, creating a turbulent boundary layer on the heat transferelement surface can increase the heat transfer rate. In the event that asmooth heat transfer element is used, turbulence normally occurs in avery thin boundary layer, producing only a small amount of turbulentkinetic energy and resulting in less than optimal heat transfer.Therefore, to induce increase turbulent kinetic energy (and thus toincrease the heat transfer rate), a stirring mechanism that abruptlychanges the direction of velocity vectors is preferably utilized. Thiscan create high levels of turbulence intensity in the free stream (andnot just the boundary layer), thereby sufficiently increasing the heattransfer rate. If the flow of blood is continuous (non-pulsatile) flow(such as encountered in venous flow), this turbulence or mixingintensity should be maintained at all times. In the event that bloodflow is pulsatile flow (such as is encountered in arterial flow), themixing intensity should be maintained over a majority of the pulsatileperiod (e.g., the cardiac cycle).

To create the desired level of mixing intensity in the blood freestream, in one preferred embodiment, the heat transfer element isprovided with a modular design. This design creates helical blood flowand produces a high level of mixing in the free stream by periodicallyforcing abrupt changes in the direction of the helical blood flow. FIG.2 is a perspective view of such a mixing inducing heat transfer elementwithin a blood vessel. Mixed flow is indicated at point 114, in the freestream area. The abrupt changes in flow direction are achieved throughthe use of a series of two or more heat transfer segments, eachcomprised of one or more helical ridges.

The use of periodic abrupt changes in the helical direction of the bloodflow in order to induce strong free stream turbulence or mixing may beillustrated with reference to a common clothes washing machine. Therotor of a washing machine spins initially in one direction causinglaminar flow. When the rotor abruptly reverses direction, significantturbulent kinetic energy is created within the entire washbasin as thechanging currents cause random turbulent motion within the clothes-waterslurry.

FIG. 3 is an elevation view of one embodiment of a heat transfer element14. The heat transfer element 14 is comprised of a series of elongated,articulated segments or modules 20, 22, 24. Three such segments areshown in this embodiment, but one or more such segments could be usedwithout departing from the spirit of the invention. As seen in FIG. 3, afirst elongated heat transfer segment 20 is located at the proximal endof the heat transfer element 14. A mixing-inducing exterior surface ofthe segment 20 comprises four parallel helical ridges 38 with fourparallel helical grooves 26 therebetween. One, two, three, or moreparallel helical ridges 38 could also be used. In this embodiment, thehelical ridges 38 and the helical grooves 26 of the heat transfersegment 20 have a left hand twist, referred to herein as acounter-clockwise spiral or helical rotation, as they proceed toward thedistal end of the heat transfer segment 20.

The first heat transfer segment 20 is coupled to a second elongated heattransfer segment 22 by a first bellows section 25, which providesflexibility and compressibility. The second heat transfer segment 22comprises one or more helical ridges 32 with one or more helical grooves30 therebetween. The ridges 32 and grooves 30 have a right hand, orclockwise, twist as they proceed toward the distal end of the heattransfer segment 22. The second heat transfer segment 22 is coupled to athird elongated heat transfer segment 24 by a second bellows section 27.The third heat transfer segment 24 comprises one or more helical ridges36 with one or more helical grooves 34 therebetween. The helical ridge36 and the helical groove 34 have a left hand, or counter-clockwise,twist as they proceed toward the distal end of the heat transfer segment24. Thus, successive heat transfer segments 20, 22, 24 of the heattransfer element 14 alternate between having clockwise andcounterclockwise helical twists. The actual left or right hand twist ofany particular segment is immaterial, as long as adjacent segments haveopposite helical twist.

In addition, the rounded contours of the ridges 38, 32, 36 also allowthe heat transfer element 14 to maintain a relatively atraumaticprofile, thereby minimizing the possibility of damage to the bloodvessel wall.

The bellows sections 25,27 are formed from seamless and nonporousmaterials, typically metals such as nickel, copper, etc. The structureof the bellows sections 25, 27 allows them to bend, extend and compress,which increases the flexibility of the heat transfer element 14 so thatit is more readily able to navigate through blood vessels. The bellowssections 25, 27 also provide for axial compression of the heat transferelement 14, which can limit the trauma when the distal end of the heattransfer element 14 abuts a blood vessel wall. The bellows sections 25,27 are also able to tolerate cryogenic temperatures without a loss ofperformance.

It may be desirable to treat the surfaces of the heat transfer element14 to avoid clot formation. In particular, one may wish to treat thebellows sections 25, 27 because stagnation of the blood flow may occurin the convolutions, thus allowing clots to form and cling to thesurface to form a thrombus. One means by which to prevent thrombusformation is to bind an antithrombogenic agent to the surface of theheat transfer element 14. For example, heparin is known to inhibit clotformation and is also known to be useful as a biocoating. Alternatively,the surfaces of the heat transfer element 14 may be bombarded with ionssuch as nitrogen. Bombardment with nitrogen can harden and smooth thesurface and thus prevent adherence of clotting factors to the surface.

FIG. 4 is a longitudinal sectional view of the heat transfer element 14of an embodiment of the invention, taken along line 5-5 in FIG. 3. Someinterior contours are omitted for purposes of clarity. An inner tube 42creates an inner coaxial lumen 42 and an outer coaxial lumen 46 withinthe heat transfer element 14. Once the heat transfer element 14 is inplace in the blood vessel, a working fluid such as saline or otheraqueous solution may be circulated through the heat transfer element 14.Fluid flows up a supply catheter into the inner coaxial lumen 40. At thedistal end of the heat transfer element 14, the working fluid exits theinner coaxial lumen 40 and enters the outer lumen 46. As the workingfluid flows through the outer lumen 46, heat is transferred from theworking fluid to the exterior surface 37 of the heat transfer element14, or vice versa. Because the heat transfer element 14 is constructedfrom a high conductivity material, the temperature of its exteriorsurface 37 may reach very close to the temperature of the working fluid.The tube 42 may be formed as an insulating divider to thermally separatethe inner lumen 40 from the outer lumen 46. For example, insulation maybe achieved by creating longitudinal air channels in the wall of theinsulating tube 42. Alternatively, the insulating tube 42 may beconstructed of a non-thermally conductive material likepolytetrafluoroethylene or some other polymer.

The same mechanisms that govern the heat transfer rate between theexterior surface 37 of the heat transfer element 14 and the blood alsogovern the heat transfer rate between the working fluid and the interiorsurface 38 of the heat transfer element 14. The heat transfercharacteristics of the interior surface 38 are particularly importantwhen using water, saline or other fluid that remains a liquid as thecoolant. Other coolants such as Freon undergo nucleate boiling andcreate turbulence through a different mechanism. Saline is a safecoolant because it is non-toxic, and leakage of saline does not resultin a gas embolism, which could occur with the use of boilingrefrigerants. Since turbulence or mixing in the coolant is enhanced bythe shape of the interior surface 38 of the heat transfer element 14,the coolant can be delivered to the heat transfer element 14 at a warmertemperature and still achieve the necessary heat transfer rate.

Further details and embodiments concerning the heat transfer elementdesign and operation can be found in commonly assigned WO 99/48449, thecomplete disclosure of which is incorporated by reference.

In a further embodiment of the invention, the heat transfer element ismade of a flexible material, such as latex rubber. The latex rubberprovides a high degree of flexibility which was previously achieved byarticulation. The latex rubber further allows the heat transfer elementto be made collapsible so that when deflated the same may be easilyinserted into an artery. Insertion and location may be conveniently madeby way of a guide catheter or guide wire. Following insertion andlocation in the desired artery, the heat transfer element may beinflated for use by a working fluid such as saline, water,perfluorocarbons, or other suitable fluids.

A heat transfer element made of a flexible material generally hassignificantly less thermal conductivity than a heat transfer elementmade of metal. The device compensates for this by enhancing the surfacearea available for heat transfer. This may be accomplished in two ways:by increasing the cross-sectional size and by increasing the length.Regarding the former, the device may be structured to be large wheninflated, because when deflated the same may still be inserted into anartery. In fact, the device may be as large as the arterial wall, solong as a path for blood flow is allowed, because the flexibility of thedevice tends to prevent damage to the arterial wall even upon contact.Such paths are described below. Regarding the latter, the device may beconfigured to be long. One way to configure a long device is to taperthe same so that the device may fit into distal arteries having reducedradii in a manner described below. The device further compensates forthe reduced thermal conductivity by reducing the thickness of the heattransfer element wall.

Embodiments of the device use a heat transfer element design thatproduces a high level of turbulence in the free stream of the blood andin the working fluid. One embodiment of the invention forces a helicalmotion on the working fluid and imposes a helical barrier in the blood,causing turbulence. In an alternative embodiment, the helical barrier istapered. In a second alternative embodiment, a tapered inflatable heattransfer element has surface features to cause turbulence. As oneexample, the surface features may have a spiral shape. In anotherexample, the surface features may be staggered protrusions. In all ofthese embodiments, the design forces a high level of turbulence in thefree stream of the blood by causing the blood to navigate a tortuouspath while passing through the artery. This tortuous path causes theblood to undergo violent accelerations resulting in turbulence.

In a third alternative embodiment of the invention, a taper of aninflatable heat transfer element provides enough additional surface areaper se to cause sufficient heat transfer. In all of the embodiments, theinflation is performed by the working fluid, such as water or saline.

Referring to FIG. 5, a side view is shown of a first embodiment of aheat transfer element 14 according to an embodiment of the invention.The heat transfer element 14 is formed by an inlet lumen 22 and anoutlet lumen 20. In this embodiment, the outlet lumen 20 is formed in ahelix shape surrounding the inlet lumen 22 that is formed in a pipeshape. The names of the lumens are of course not limiting. It will beclear to one skilled in the art that the inlet lumen 22 may serve as anoutlet and the outlet lumen 20 may serve as an inlet. It will also beclear that the heat transfer element is capable of both heating (bydelivering heat to) and cooling (by removing heat from) a desired area.

The heat transfer element 14 is rigid but flexible so as to beinsertable in an appropriate vessel by use of a guide catheter.Alternatively, the heat transfer element may employ a device forthreading a guide wire therethrough to assist placement within anartery. The heat transfer element 14 has an inflated length of L, ahelical diameter of D_(c), a tubal diameter of d, and a helical angle ofα. For example, D_(c) may be about 3.3 mm and d may be about 0.9 mm to 1mm. Of course, the tubal diameter d need not be constant. For example,the diameter of the inlet lumen 22 may differ from that of the outletlumen 20.

The shape of the outlet lumen 20 in FIG. 5 is helical. This helicalshape presents a cylindrical obstacle, in cross-section, to the flow ofblood. Such obstacles tend to create turbulence in the free stream ofblood. In particular, the form of turbulence is the creation of vonKarman vortices in the wake of the flow of blood, downstream of thecylindrical obstacles.

Typical inflatable materials are not highly thermally conductive. Theyare much less conductive than the metallic heat transfer elementdisclosed in the patent application incorporated by reference above. Thedifference in conductivity is compensated for in at least two ways inthe present device. The material is made thinner and the heat transferelement is afforded a larger surface area. Regarding the former, thethickness may be less than about ½ mil for adequate cooling.

Thin inflatable materials, particularly those with large surface areas,may require a structure, such as a wire, within their interiors tomaintain their approximate uninflated positions so that upon inflation,the proper form is achieved. Thus, a wire structure 67 is shown in FIG.5 which may be advantageously disposed within the inflatable material toperform such a function.

Another consideration is the angle α. of the helix. Angle α should bedetermined to optimize the helical motion of the blood around the lumens20 and 22, enhancing heat transfer. Of course, angle α should also bedetermined to optimize the helical motion of the working fluid withinthe lumens 20 and 22. The helical motion of the working fluid within thelumens 20 and 22 increases the turbulence in the working fluid bycreating secondary motions. In particular, helical motion of a fluid ina pipe induces two counter-rotating secondary flows.

An enhancement of h_(c) would be obtained in this system, and thisenhancement may be described by a Nusselt number Nu of up to about 10 oreven more.

The above discussion describes one embodiment of a heat transferelement. An alternative embodiment of the device, shown in a side viewin FIG. 6, illustrates a heat transfer element 41 with a surface areaenhancement. Increasing the surface area of the inflatable materialenhances heat transfer. The heat transfer element 14 includes a seriesof coils or helices of different coil diameters and tubal diameters. Itis not strictly necessary that the tubal diameters differ, but it islikely that commercially realizable systems will have differing tubaldiameters. The heat transfer element 14 may taper either continuously orsegmentally.

This alternative embodiment enhances surface area in two ways. First,the use of smaller diameter lumens enhances the overallsurface-to-volume ratio. Second, the use of progressively smaller (i.e.,tapered) lumens allows a distal end 69 to be inserted further into anartery than would be possible with the embodiment of FIG. 5.

In the embodiment of FIG. 6, a first coil segment 42 is shown havinglength L₁ and diameter D_(C1). The first coil segment 42 is formed of aninlet lumen 51 having diameter d₁ and an outlet lumen 53 having diameterd_(1′). In the first coil segment, as well as the others, the outletlumen need not immediately drain the inlet lumen. In FIG. 6, the inletlumen for each segment feeds the inlet lumen of the succeeding segmentexcept for an inlet lumen adjacent a distal end 69 of the heat transferelement 41 which directly feeds its corresponding outlet lumen.

A separate embodiment may also be constructed in which the inlet lumenseach provide working fluid to their corresponding outlet lumens. In thisembodiment, either a separate lumen needs to be provided to drain eachoutlet lumen or each outlet lumen rains into the adjacent outlet lumen.This embodiment has the advantage that an opposite helicity may beaccorded each successive segment. The opposite helicities in turnenhance the turbulence of the working fluid flowing past them. A secondcoil segment 44 is shown having length L₂ and diameter D_(c2). Thesecond coil segment 44 is formed of an inlet lumen 55 having diameter d₂and an outlet lumen 57 having diameter d₂. A third coil segment 46 isshown having length L₃ and diameter D_(C3). The third coil segment 46 isformed of an inlet lumen 59 having diameter d₃ and an outlet lumen 61having diameter d_(3′). Likewise, a fourth coil segment 48 is shownhaving length L₄ and diameter D_(C4). The fourth coil segment 48 isformed of an inlet lumen 63 having diameter d₄ and an outlet lumen 65having diameter d_(4′). The diameters of the lumens, especially that ofthe lumen located at or near distal end 69, should be large enough tonot restrict the flow of the working fluid within them. Of course, anynumber of lumens may be provided depending on the requirements of theuser.

FIG. 7 shows the connection between two adjacent inlet lumens 51 and 55.A joint 167 is shown coupling the two lumens. The construction of thejoint may be by way of variations in stress, hardening, etc.

An advantage to this alternative embodiment arises from the smallerdiameters of the distal segments. The heat transfer element of FIG. 6may be placed in smaller workspaces than the heat transfer element ofFIG. 5. For example, a treatment for brain trauma may include placementof a cooling device in the internal carotid artery of a patient. Asnoted above, the common carotid artery feeds the internal carotidartery. In some patients, the heat transfer element of FIG. 5 may notfit in the internal carotid artery. Similarly, the first coil segment ofthe heat transfer element in FIG. 6 may not easily fit in the internalcarotid artery, although the second, third, and fourth segments may fit.Thus, in the embodiment of FIG. 6, the first coil segment may remain inthe common carotid artery while the segments of smaller diameter (thesecond, third, and fourth) may be placed in the internal carotid artery.In fact, in this embodiment, D_(c1), may be large, such as 5-6 mm. Theoverall length of the heat transfer element 41 may be, e.g., about 20 to25 cm.

An additional advantage was mentioned above. The surface area of thealternative embodiment of FIG. 6 may be substantially larger than thatof the embodiment of FIG. 5, resulting in significantly enhanced heattransfer. For example, the enhancement in surface area may besubstantial, such as up to or even more than three times compared to thesurface area of the device of the application incorporated by referenceabove. An additional advantage of both embodiments is that the helicalrounded shape allows a traumatic insertion into cylindrical cavitiessuch as, e.g., arteries.

The embodiment of FIG. 6 may result in an Nu from 1 up to about 50.

FIG. 8 shows a second alternative embodiment of the device employingsurface features rather than overall shape to induce turbulence. Inparticular, FIG. 8 shows a heat transfer element 201 having an inletlumen (not shown) and an outlet inflatable lumen 220 having foursegments 203, 205,207, and 221. Segment 203 is adjacent a proximal end211 and segment 221 is adjacent a distal end 213. The segments arearranged having reducing radii in the direction of the proximal end tothe distal end. In a manner similar to that of the embodiment of FIG. 6,the feature of reducing radii allows insertion of the heat transferelement into small work places such as small arteries.

Heat transfer element 201 has a number of surface features 215 disposedthereon. The surface features 215 may be constructed with, e.g., varioushardening treatments applied to the heat transfer element 201, oralternatively by injection molding. The hardening treatments may resultin a wavy or corrugated surface to the exterior of heat transfer element201. The hardening treatments may further result in a wavy or corrugatedsurface to the interior of heat transfer element 201. FIG. 9 shows avariation of this embodiment, in which a fabrication process is usedwhich results in a spiral or helical shape to the surface features.

The embodiment of FIG. 8 may result in an Nu of about 1 to 50.

In another variation of this embodiment, shown in FIG. 10, a heattransfer element 150 employs a plurality of protrusions 154 on outletlumen 152 which surrounds an inlet lumen 158. In particular, FIG. 10 isa cut-away perspective view of an alternative embodiment of a heattransfer element 150. A working fluid is circulated through an inletlumen 156 to a distal tip of the heat transfer element 150 therebyinflating the heat transfer element 150. The working fluid thentraverses an outlet coaxial lumen 160 in order to transfer heat from theexterior surface 152 of the heat transfer element 150. The insidestructure of the heat transfer element 150 is similar to the exteriorstructure in order to induce turbulent flow of the working fluid.

An external surface 152 of the inflatable heat transfer element 150 iscovered with a series of staggered protrusions 154. The staggered natureof the protrusions 154 is readily seen with reference to FIG. 11 whichis a transverse cross-sectional view of an inflated heat transferelement taken along the line 8-8 in FIG. 10. In order to induce freestream turbulence, the height, d_(p), of the staggered protrusions 154is greater than the thickness of the boundary layer which would developif a smooth heat transfer element had been introduced into the bloodstream. As the blood flows along the external surface 152, it collideswith one of the staggered protrusions 154 and a turbulent flow iscreated. As the blood divides and swirls along side of the firststaggered protrusion 154, it collides with another staggered protrusion154 within its path preventing the re-lamination of the flow andcreating yet more turbulence. In this way, the velocity vectors arerandomized and free stream turbulence is created. As is the case withthe other embodiments, this geometry also induces a turbulent effect onthe internal coolant flow.

The embodiment of FIG. 10 may result in an Nu of about 1 to 50.

Of course, other surface features may also be used which result inturbulence in fluids flowing past them. These include spirals, helices,protrusions, various polygonal bodies, pyramids, tetrahedrons, wedges,etc.

In some situations, an enhanced surface area alone, without the creationof additional turbulence, may result in sufficient heat transfer to coolthe blood. Referring to FIG. 12, a heat transfer element 302 is shownhaving an inlet lumen 304 and an outlet lumen 306. The inlet lumen 304provides a working fluid to the heat transfer element 302 and outletlumen 306 drains the working fluid from the same. The functions may, ofcourse, be reversed. The heat transfer element 302 is further dividedinto five segments, although more or less may be provided as dictated byrequirements of the user. The five segments in FIG. 12 are denotedsegments 308,310,312,314, and 316. In FIG. 12, the segment 308 has afirst and largest radius R₁, followed by corresponding radii forsegments 310, 312, 314, and 316. Segment 316 has a second and smallestradius. The length of the segment 308 is L₁, followed by correspondinglengths for segments 310, 312, 314, and 316.

A purely tapered (nonsegmented) form may replace the tapered segmentalform, but the former may be more difficult to manufacture. In eithercase, the tapered form allows the heat transfer element 302 to bedisposed in small arteries, i.e., arteries with radii smaller than R₁. Asufficient surface area is thus afforded even in very small arteries toprovide the required heat transfer.

The surface area and thus the size of the device should be substantialto provide the necessary heat transfer. Example dimensions for athree-segmented tapered form may be as follows: L₁=10 cm, R₁=2.5 mm;L₂=10 cm, R₂=1.65 mm, L₃=5 cm, R₃=1 mm. Such a heat transfer elementwould have an overall length of 25 cm and a surface area of 3×10⁴ m.

The embodiment of FIG. 12 results in an enhancement of the heat transferrate of up to about 300% due to the increased surface area S alone.

A variation of the embodiment of FIG. 12 includes placing at least oneturbulence-inducing surface feature within the interior of the outletlumen 306. This surface feature may induce turbulence in the workingfluid, thereby increasing the convective heat transfer rate in themanner described above.

Another variation of the embodiment of FIG. 12 involves reducing thejoint diameter between segments (not shown).

For example, the inflatable material may be formed such that joints 318,320, 322, and 324 have a diameter only slightly greater than that of theinlet lumen 304. In other words, the heat transfer element 302 has atapered “sausage” shape.

In all of the embodiments, the inflatable material may be formed fromseamless and nonporous materials which are therefore impermeable to gas.Impermeability can be particularly important depending on the type ofworking fluid which is cycled through the heat transfer element. Forexample, the inflatable material may be latex or other such rubbermaterials, or alternatively of any other material with similarproperties under inflation. The flexible material allows the heattransfer element to bend, extend and compress so that it is more readilyable to navigate through tiny blood vessels. The material also providesfor axial compression of the heat transfer element which can limit thetrauma when the distal end of the heat transfer element 14 abuts a bloodvessel wall. The material should be chosen to tolerate temperatures inthe range of −1° C. to 37° c., or even higher in the case of bloodheating, without a loss of performance.

It may be desirable to treat the surface of the heat transfer element toavoid clot formation because the heat transfer element may dwell withinthe blood vessel for extended periods of time, such as 24-48 hours oreven longer. One means by which to prevent thrombus formation is to bindan antithrombogenic agent to the surface of the heat transfer element.For example, heparin is known to inhibit clot formation and is alsoknown to be useful as a biocoating.

Referring back to FIG. 5, an embodiment of the method of the inventionwill be described. A description with reference to the embodiment ofFIG. 6 is analogous. A guide catheter or wire may be disposed up to ornear the area to be cooled or heated. The case of a guide catheter willbe discussed here. The heat transfer element may be fed through theguide catheter to the area. Alternatively, the heat transfer element mayform a portion of the guide catheter. A portion of the interior of theguide catheter may form, e.g., the return lumen for the working fluid.In any case, the movement of the heat transfer element is madesignificantly more convenient by the flexibility of the heat transferelement as has been described above.

Once the heat transfer element 14 is in place, a working fluid such assaline or other aqueous solution may be circulated through the heattransfer element 14 to inflate the same. Fluid flows from a supplycatheter into the inlet lumen 22. At the distal end 26 of the heattransfer element 14 the working fluid exits the inlet lumen 22 andenters the outlet lumen 20.

In the case of the embodiment of FIG. 8, for which the description ofFIG. 10 is analogous, the working fluid exits the inlet lumen and entersan outlet inflatable lumen 220 having segments 203, 205, 207, and 221.As the working fluid flows through the outlet lumen 220, heat istransferred from the exterior surface of the heat transfer element 201to the working fluid. The temperature of the external surface may reachvery close to the temperature of the working fluid because the heattransfer element 201 is constructed from very thin material.

The working fluids that may be employed in the device include water,saline or other fluids which remain liquid at the temperatures used.Other coolants, such as freon, undergo nucleated boiling and may createturbulence through a different mechanism. Saline is a safe coolantbecause it is non-toxic and leakage of saline does not result in a gasembolism which may occur with the use of boiling refrigerants.

By enhancing turbulence in the coolant, the coolant can be delivered tothe heat transfer element at a warmer temperature and still achieve thenecessary heat transfer rate. In particular, the enhanced heat transfercharacteristics of the internal structure allow the working fluid to bedelivered to the heat transfer element at lower flow rates and lowerpressures. This is advantageous because high pressures may stiffen theheat transfer element and cause the same to push against the wall of thevessel, thereby shielding part of the heat transfer unit from the blood.Such pressures are unlikely to damage the walls of the vessel because ofthe increased flexibility of the inflated device. The increased heattransfer characteristics allow the pressure of the working fluid to bedelivered at pressures as low as 5 atmospheres, 3 atmospheres, 2atmospheres or even less than 1 atmosphere.

In a preferred embodiment, the heat transfer element creates aturbulence intensity greater than 0.05 in order to create the desiredlevel of turbulence in the entire blood stream during the whole cardiaccycle. The turbulence intensity may be greater than 0.055, 0.06, 0.07 orup to 0.10 or 0.20 or even greater.

FIG. 13 is a schematic representation of the device being used to coolthe brain of a patient. The selective organ hypothermia apparatusincludes a working fluid supply 16, preferably supplying a chilledliquid such as water, alcohol or a halogenated hydrocarbon, a supplycatheter 12 and the heat transfer element 15. The heat transfer element15 may have the form, e.g., of any of the embodiments above or ofsimilar such heat transfer elements. The supply catheter 12 has acoaxial construction. An inlet lumen within the supply catheter 12receives coolant from the working fluid supply 16. The coolant travelsthe length of the supply catheter 12 to the heat transfer element 15which serves as the cooling tip of the catheter. At the distal end ofthe heat transfer element 15, the coolant exits the insulated interiorlumen and traverses the length of the heat transfer element 15 in orderto decrease the temperature of the heat transfer element 15. The coolantthen traverses an outlet lumen of the supply catheter 12, which may havea helical or other shape as described above. The supply catheter 12 is aflexible catheter having a diameter sufficiently small to allow itsdistal end to be inserted percutaneously into an accessible artery suchas the femoral artery of a patient. The supply catheter 12 issufficiently long to allow the heat transfer element 15 to be passedthrough the vascular system of the patient and placed in the internalcarotid artery or other small artery. If the heat transfer element 15employs tapering as in some of the embodiments described above, the samemay be placed in very small arteries without damage to the arterialwalls.

The heat transfer element can absorb or provide over 75 watts of heat tothe blood stream and may absorb or provide as much as 100 watts, 150watts, 170 watts or more. For example, a heat transfer element with adiameter of 4 mm and a length of approximately 10 cm, using ordinarysaline solution chilled so that the surface temperature of the heattransfer element is approximately 5° C. and pressurized at 2atmospheres, can absorb about 150 watts of energy from the bloodstream.Smaller geometry heat transfer elements may be developed for use withsmaller organs which provide 60 watts, 50 watts, 25 watts or less ofheat transfer.

Although the present invention has been described with respect toseveral exemplary embodiments, there are many other variations of theabove-described embodiments that will be apparent to those skilled inthe art. It is understood that these variations are within the teachingof the present invention, which is to be limited only by the claimsappended hereto.

1. A coronary bypass procedure comprising: positioning a heat transferelement in a blood vessel of a patient, wherein the heat transferelement comprises: an inlet lumen to introduce a circulating workingfluid; and an outlet lumen to extract a circulating working fluid, theoutlet lumen having a helical shape to induce turbulence in bloodflowing past the outlet lumen and in the working fluid; cooling the bodyof the patient to less than 35° C. using said heat transfer element; andforming a fluid communicating graft between an arterial blood supply andthe coronary artery; wherein the patient's blood is oxygenated with thepatient's lungs and wherein blood is circulated using the patient'sheart or using an intracorporeal pump.
 2. The coronary bypass procedureof claim 1, wherein the heat transfer element absorbs at least 150 Wattsof heat during cooling.
 3. The coronary bypass procedure of claim 1,further comprising warming the body of the patient to about 37° C. usingsaid heat transfer element, subsequent to the step of forming the fluidcommunicating graft.
 4. The coronary bypass procedure of claim 1,wherein the step of forming a fluid communicating graft between thearterial blood supply and the coronary artery is preformed on a beatingheart during bradycardia of the heart.
 5. The coronary bypass procedureof claim 1, wherein the heart is arrested or nearly arrested during atleast a portion of the step of forming the fluid communicating graft. 6.The coronary bypass procedure of claim 5, wherein the heart ischemically arrested.
 7. The coronary bypass procedure of claim 5,wherein the heart is electrically arrested.
 8. The coronary bypassprocedure of claim 5, wherein the patient's circulation is supportedwith a pump positioned in the patient's vasculature.
 9. The coronarybypass procedure of claim 8, wherein the pump is at least partiallypositioned in the left ventricle.
 10. The coronary bypass procedure ofclaim 9, wherein the pump is introduced through the femoral artery. 11.The coronary bypass procedure of claim 1, wherein the heartbeat isintermittently arrested and stimulated; and wherein at least a portionof the step of forming the fluid communicating graft is carried outduring periods of heartbeat arrest.
 12. The coronary bypass procedure ofclaim 11, wherein the heart is chemically arrested and wherein theheartbeat is electrically stimulated.
 13. The coronary bypass procedureof claim 12, wherein the heart is chemically arrested using one or morebeta-blockers.
 14. The coronary bypass procedure of claim 11, whereinthe heart is electrically arrested and electrically stimulated.
 15. Thecoronary bypass procedure of claim 1, wherein the heat transfer elementis positioned in the venous vasculature.
 16. The coronary bypassprocedure of claim 15, wherein the heat transfer element is positionedin the inferior vena cava.
 17. The coronary bypass procedure of claim16, wherein the heat transfer element is introduced into the femoralvein.
 18. The coronary bypass procedure of claim 17, wherein the heattransfer element is about 4 to 5 mm in diameter.
 19. The catheter systemof claim 1, wherein the inlet lumen and the outlet lumen are made of aflexible material.
 20. The catheter system of claim 19, wherein theflexible material is rubber.
 21. The catheter system of claim 19,wherein the flexible material is a material capable of undergoinginflation.
 22. The catheter system of claim 1, further comprising morethan one outlet lumen, each outlet lumen having a helical shape.
 23. Thecatheter system of claim 1, wherein the working fluid is saline.
 24. Thecatheter system of claim 1, wherein the helical shape of the outletlumen is tapered when inflated.
 25. The catheter system of claim 24,wherein the helical shape of the outlet lumen is segmentally taperedwhen inflated.
 26. The catheter system of claim 1, wherein a radius ofthe inlet lumen decreases such that the inlet lumen is tapered wheninflated.
 27. The catheter system of claim 1, wherein a radius of theoutlet lumen decreases such that the outlet lumen is tapered wheninflated.
 28. The catheter system of claim 1, wherein the helical shapeof the outlet lumen is structured and shaped to have a geometry so as toinduce turbulence within a free stream of blood flow when disposed in ablood vessel.
 29. The catheter system of claim 1, wherein the inletlumen is substantially straight.
 30. The catheter system of claim 1,wherein the outlet lumen helically encircles the inlet lumen.
 31. Thecoronary bypass procedure of claim 1, wherein the use of acardiopulmonary bypass system and obstruction of the ascending aorta areavoided.
 32. The coronary bypass procedure of claim 1, wherein the bodyof the patient is cooled to 32±2° C. using said heat transfer element.33. The coronary bypass procedure of claim 6, wherein the heart isarrested using a beta-blocker.
 34. A hypothermic medical procedurecomprising: administering a beta-blocking drug to a patient; deliveringa heat transfer element to a blood vessel of the patient, wherein theheat transfer element comprises: an inlet lumen to introduce acirculating working fluid; and an outlet lumen to extract a circulatingworking fluid, the outlet lumen having a helical shape to induceturbulence in blood flowing past the outlet lumen and in the workingfluid; and cooling a region of the patient or the body of the patient toless than 35° C. using said heat transfer element while said patient isin a conscious or semiconscious state.
 35. The procedure of claim 34,wherein the beta-blocking drug is a ∃1 blocker.
 36. The procedure ofclaim 35, wherein the 31 blocker is selected from one or more ofacebutolol, atenolol, betaxolol, bisoprolol, esmolol and metoprolol. 37.The procedure of claim 34, wherein the beta-blocking drug is a ∃1∃2blocker.
 38. The procedure of claim 37, wherein the ∃1∃2 blocker isselected from one or more of carteolol, nadolol, penbutolol, pindolol,propranolol, sotalol and timolol.
 39. The procedure of claim 34, whereinthe beta-blocking drug is an ∀∃1∃2 blocker.
 40. The procedure of claim37, wherein the ∀∃1∃2 blocker is selected from one or more of carvediloland labetalol.
 41. The procedure of claim 34, wherein the beta-blockingdrug is administered after delivering the heat transfer element.
 42. Theprocedure of claim 34, wherein the body of the patient is cooled. 43.The procedure of claim 34, wherein an organ of the patient is cooled.